The belief that all primary follicles in adult mammalian females were formed during the fetal period has persisted for over fifty years, primarily due to the diminution in the number of primary follicles that occurs with age. Recent studies, however, have brought this belief into question.
Bukovsky, et al, Am. J. Reprod. Immunol., 33:323-340 (1995), reported that the ovarian surface epithelium (OSE) is a source of germ cells in adult human females. Bukovsky, et al, Reprod. Biol. Endocrinol., 2:20 (2004) reported that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the human ovarian cortex during adulthood.
These studies have suggested that the hypothesis that all primary follicles in adult human females were formed during the fetal period is incorrect. Rather, these studies indicate that primary follicles that were formed during the fetal period may persist for some time, perhaps through childhood, and then starting with menarche, new cohorts of primary follicles replace the fetal follicles that undergo atresia. Moreover, it is suggested that during each successive menstrual cycle until about the age of 38, fresh follicles are produced that replace older follicles. At about the age of 38±2 years, formation of new primary follicles ceases, possibly due to the onset of immune senescence (certain immune system-related cells appear to be required for the formation of new germ cells from the OSE), and the aging follicles accumulate genetic alterations until exhausted at the onset of natural menopause.
In recent years, women in developed countries have an increased tendency to delay having a first child. Reasons for waiting to start a family include the desire to wait until the family has financial security and the desire of women to commit to their marriages and to their careers before focusing their energy on children. According to the National Center for Health Statistics, the birth rate for women aged 40-45 years rose 20% between 1990 and 1995, and increased 74% during 1981-95. The rising birth rate along with the increasing number of women in this age group means that there were more babies born in 1995 to mothers in their 40s than in any year since 1966.
A significant problem that occurs due to delayed parenting is that often women over the age of 40 have a greatly decreased chance of becoming pregnant. Much of this difficulty stems from a decrease in the availability of oocytes that are available for fertilization. Additionally, women below the age of 40 that have premature ovarian failure are unable to become pregnant due to the lack of production of oocytes.
A woman who desires to become pregnant but who does not produce her own oocytes may elect to undergo a procedure referred to as in-vitro fertilization (IVF) in which eggs donated from another woman are fertilized in vitro and then one or two of the resultant developing embryos are implanted into her uterus. Of course, the resultant child from this procedure will be genetically unrelated to the woman undergoing this procedure. At the present time, there are no procedures available by which a woman who does not produce oocytes is able to produce a child who is genetically related to her.
An important need exists for the development of methodologies that will permit a woman who does not produce oocytes that have the potential to develop into an offspring who is genetically related to her.